Slit3 Secreted from M2-like Macrophages Increases Sympathetic Activity and Thermogenesis in Adipose Tissue

Overview

Journal Nat Metab

Publisher Springer Nature

Specialty Endocrinology

Date 2021 Nov 16

PMID 34782792

Citations 45

Authors

Yi-Na Wang

Yan Tang

Zhihui He

Hong Ma

Linyuan Wang

Yang Liu

Qiqi Yang

Dongning Pan

Cuiqing Zhu

Shuwen Qian

Qi-Qun Tang

Affiliations

Soon will be listed here.

Abstract

Beiging of white adipose tissue (WAT) is associated with an increase of anti-inflammatory M2-like macrophages in WAT. However, mechanisms through which M2-like macrophages affect beiging are incompletely understood. Here, we show that the macrophage cytokine Slit3 is secreted by adipose tissue macrophages and promotes cold adaptation by stimulating sympathetic innervation and thermogenesis in mice. Analysing the transcriptome of M2-like macrophages in murine inguinal WAT (iWAT) after cold exposure, we identify Slit3 as a secreted cytokine. Slit3 binds to the ROBO1 receptor on sympathetic neurons to stimulate Ca/calmodulin-dependent protein kinase II signalling and norepinephrine release, which enhances adipocyte thermogenesis. Adoptive transfer of Slit3-overexpressing M2 macrophages to iWAT promotes beiging and thermogenesis, whereas mice that lack Slit3 in myeloid cells are cold-intolerant and gain more weight. Our findings shed new light on the integral role of M2-like macrophages for adipose tissue homeostasis and uncover the macrophage-Slit3-sympathetic neuron-adipocyte signalling axis as a regulator of long-term cold adaptation.

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